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Summary
Summit Therapeutics (NASDAQ:SMMT) reported disappointing results for their lead asset, ridinilazole which is unlikely to generate significant revenue if ever approved. The company is in early stage testing of its antibiotic which has activity against Enterobacteriaceae, a pathogen which is increasingly resistant to standard antibiotics. The company is a few years away from proof of concept human efficacy data for this asset, SMT-737. Given the difficulty of focusing on anti-infectives, the company has made a decision to expand into the microbiome and/or oncology through business development.
Ridinilazole is unlikely to be widely prescribed
Summit Therapeutics announced that they met with the FDA to discuss results of the CoDIFy Phase III clinical trials. The trials were pivotal trials comparing ridinilazole to vancomycin and designed to show superiority over one of the current standard of care antibiotics, vancomycin. In the clinical trials conducted to date, ridinilazole failed to show superiority over vancomycin. Summit was advised that an additional clinical trial would be required and they plan to explore this possibility. The company described the pathway as requiring “reasonable efforts.“
The real issue however is that fidaxomicin, an antibiotic marketed by Merck was tested and was shown to be non-inferior to vancomycin in clinical response at the end of treatment and superior to vancomycin in sustained clinical cure at 25 days post treatment. Sustained cure rates in pivotal trials were 70% and 72 % for fidaxomicin vs 57% for vancomycin at day 25.
For a first episode of C. difficile infection (CDI), Infectious Disease Society of America (IDSA) now recommends a standard course or a pulsed course of fidaxomicin as the preferred choice. Fidaxomicin, which is highly effective, will likely be generically available by 2028 making ridinilazole unlikely to be widely prescribed.
In addition, Acurx Pharmaceuticals (ACXP) is developing ibezapolstat, an antibiotic for CDI. A 100 percent cure rate at day 12 was observed with no recurrence at day 38 in all of the 10 patients treated in the phase 2A trial. In addition, there were no treatment discontinuations and no SAEs. One patient out of the ten treated patients reported nausea. Of the 10 treated patients in the phase 2A trial, 86% of the stool samples tested were positive for C. difficile growth at day 1 but by day 3 of treatment and at every time point thereafter, no C. difficile was detected in stool.
This indicates a rapid onset and swift eradication of C. difficile. Further clinical trials are now underway but if this profile is verified in the ongoing Phase 2B testing, ibezapolstat may be a preferred drug to treat CDI. Given the competitive landscape, further development may only be logical if Summit Therapeutics can secure outside funding (potentially from BARDA) and if the clinical trial is relatively inexpensive to conduct.
The Pipeline- SMT-737
Summit Therapeutics estimates there are more than a million Enterobacteriaceae infections annually. Some of these infections are increasingly resistant to standard antibiotics such as penicillins and cephalosporins. The CDC has identified carbapenem-resistant Enterobacteriaceae as an urgent threat. Carbapenems are a class of antibiotics reserved for serious infections that are administered IM or IV. Resistance to these last resort antibiotics is very concerning.
SMT-737 has a unique mechanism of action which is different from existing antibiotics. IND-enabling studies are underway. In in-vitro studies (in the laboratory) SMT-737 was potent and bactericidal against multiple strains including drug resistant Enterobacteriaceae. Testing to date has been conducted in an animal model of UTI where cure of infection was observed. While this bacteria is common in the urinary tract, and UTI may be the lead indication, the drug also achieved systemic distribution and was detected in the bloodstream and lungs. Thus, it may be effective in other infections.
There is a clear unmet need for novel antibiotics to treat these infections which most commonly occur in hospitalized patients. Premium pricing would certainly be warranted given there are an estimated 2500 deaths annually from drug resistant strains.
Business Development
Summit Therapeutics reported that, “Our intention is to expand our pipeline product portfolio in the therapeutic area of oncology and/or product offerings that are designed to work in harmony with the human gut microbiome. We intend to enact this through business development activities, including possible acquisitions and/or collaborations in addition to internal research and discovery efforts.”
Pivoting beyond the development of antibiotics to more profitable niches within biotechnology is a prudent move. Developing antibiotics is a risky business with a relatively small reward given the short duration a patient takes a therapy. Most of the major pharmaceutical companies have shut down their anti-infective development programs due to the poor economics in the space. Some smaller ones such as Achaogen and Melinta went bankrupt. While the unmet need is substantial, the economics are unfavorable.
Finances
After a recent funding, Summit Therapeutics had $74 m of cash on hand. In addition, additional BARDA funding of $14 m may be available based on an existing contract. Approximately $5 m in additional CARB-X funding may also be available to the company.
Conclusions
Ridinilazole does not appear to be a particularly valuable asset. SMT-737 is too early stage to ascertain its potential. Summit has adequate funding and a very accomplished CEO, Robert Duggan, who has invested his own money in Summit Therapeutics. Mr. Duggan took a biotech and redirected it and oversaw the transformation of Pharmacyclics into a company ABBV valued at $21B. Investors may wish to wait and see what Mr. Duggan has in mind for an encore.
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